In the past few years, next-generation cancer drugs have started trickling into the clinics, including a smart inhibitor that block a specific mutant kinase (V600E-B-RAF) and antibodies that can induce T cell-mediated rejection of certain tumors (anti-CTL4 antibodies). Another promising approach is to genetically modify T cells to attack tumors and then infuse the cells into cancer patients. Indeed, this strategy is currently entering clinical trials, specifically with T cells engineered to express the chimeric antigen receptors (CARs).
Movie: Here T cells (gray) are engineered to express chimeric antigen receptors (CARs) to redirect T-cell specificity to target CD19-positive tumor cells, expressing EGFP (green). Tumor cells turn red after the T-cell attacks and kills them (propidium iodide staining). The time-lapse imaging was performed using Nikon’s BioStation. Video presented by Alex’s Lemonade Stand Foundation.
All bleeding eventually stops.
ATP production in mitochondria (purple) can lead to the formation of reactive oxygen species (ROS) that damage mitochondria. When an organelle is beyond repair, the cellular recycling system (green) kicks-in and targets them for mitophagy, a specialized form of mitochondrial degradation.
Image: A primary retinal ganglion cell expresses a red fluorescent protein targeted to mitochondria, a green fluorescent protein fused to the autophagosomal marker LC3, and a cyan fluorescent protein in the cytosol. This image reveals how autophagosomes (green) can contact individual mitochondria (purple), before their ingestion by mitophagy.
It is currently difficult for physicians to detect small tumors and the precise boundaries of tumors during surgery. Fluorescent probes have improved tumor visualization, but these probes typically have high background signal or requires hours to illuminate. Recently, Kobayashi and colleagues developed a fluorescence probe- γ-glutamyl hydroxymethyl rhodamine green- that rapidly turns fluorescent green when it interacts with cancer cells, but not normal tissue (specifically when γ-glutamyltranspeptidase on the surface of cancer cells cleaves glutamate off the probe). When the probe is sprayed onto an in vivo mouse model of ovarian cancer, the probe activates within 1 minute, illuminating tumors <1 mm in diameter.
Movie: The hydroxymethyl rhodamine green probe is sprayed on a peritoneally disseminated SHIN3 ovarian cancer in a mouse. The movie was obtained with a regular camcorder.
The Neural Tube
- the neural tube forms the brain and spinal cord
- fusion of neural groove extends rostrally and caudally
- begins at the level of 4th somite
- closes neural groove “zips up” in some species.
- humans appear to close at multiple points along the tube.
- leaves 2 openings at either end - Neuropores
- cranial neuropore closes before caudal
Failure for the neural tube to close correctly or completely results in a neural tube defect.
This transmission electron micrograph shows a Langerhans cell (purple) exiting an isolated epithelium to disseminate the HIV-1 infection. A long cytoplasmic extension of the Langerhans cell remains anchored between basal keratinocytes and contains a large vacuole with one HIV-1BaL virion (red) inside. Epithelial sheets were inoculated with the virus by centrifugation (i.e., spinoculation) for 2 hours and then fixed in Karnovsky’s fixative for electron microscopy.
Carnegie stage 13 Embryo showing neural tube and brain flexures
Rapid growth folds the neural tube forming 3 brain flexures:
- cephalic flexure - pushes mesencephalon upwards
- cervical flexure - between brain stem and spinal cord
- pontine flexure - generates 4th ventricle
Here a mouse retina is seen en face with these “J” retinal ganglion cells marked by the expression of one fluorescent protein. The millions of other entangled neurons are not marked and thus are invisible in this image. Image obtained with a confocal scanning microscope and pseudocolored.
- neural stem cells lie in the layer closest to the ventricular space, the ventricular layer
- this layer generates both neuroblasts and glioblasts
Neuroblasts - neurons arise first as neuroblasts and migrate along radial gial, their migration stops at cortical plate. Glioblasts - glia arise later as glioblasts
Both neurons and glia undergo a complex process of growth, differentiation and interaction over a long developmental time period.
Metaphase and Anaphase
Upon entry into anaphase, the mitotic spindle reorganizes dramatically: kinetochore fibers attached to chromosomes shorten, bringing chromatids toward the poles. The astral microtubules, which radiate from each spindle pole, elongate until they reach the cell surface. Meanwhile, a bundle of antiparallel microtubules, called the ‘central spindle,’ remains at the midpoint between the two poles. The central spindle and astral microtubules collaborate to position the division plane during cytokinesis.